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Biomedical subjects

David Miller

Publications and source records attributed to David Miller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Ultrafiltration in decompensated heart failure.

Fluid congestion is the hallmark of decompensated heart failure. As heart failure progresses, reduced response to diuretics is common. In these patients, ultrafiltration has been found to alleviate excess volume and improve diuretic sensitivity. Compared with diuretics, ultrafiltration provides a more predictable and safer way to achieve euvolemia with minimal electrolyte abnormalities and neurohormonal activation. The emerging familiarity and ease of use of ultrafiltration suggests that in the future this will be an important therapy for the treatment of acute and chronic volume overload associated with decompensated heart failure.

Heart Failure↗
PubMed2005

The controversy, potential and roles of spermatozoal RNA.

The majority of cellular and molecular andrologists endorse the view that the sperm is a vessel for transporting the paternal genome to the waiting egg and nothing more. Any requirement for additional spermatozoal components that enter the ooplasm apart from the paternal centriole and the soluble egg-activating factor is generally dismissed. Many studies, however, have reported RNAs in ejaculate spermatozoa and we now know that mRNAs are delivered to the egg on fertilisation. The function and utility of sperm mRNA remains essentially unexplored. Here, we examine the controversy surrounding spermatozoal mRNA carriage, the evidence refuting its presence as an artefact and how spermatozoal mRNA is leading us to suspect that, quite apart from its undoubted diagnostic potential, it might have an important role in the establishment and maintenance of a viable paternal genome.

Animals↗
PubMed2005

Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis.

In 85% of young adults with multiple sclerosis (MS), onset is a subacute clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Methods of assessing the prognosis for patients who present with a CIS have been sought, because only 30-70% of patients with a CIS develop MS. When clinically silent brain lesions are seen on MRI, the likelihood of developing MS is high. MS can be diagnosed within 3 months of CIS presentation with certain MRI and CSF criteria. Disability from MS is less likely in patients with a CIS of optic neuritis or sensory symptoms only, few or no MRI lesions, a long period to the first relapse, and no disability after the first 5 years. Development of more reliable prognostic markers will enable new treatments to be targeted for those who are most likely to benefit. We encourage continued clinical and laboratory assessment of patients with a CIS.

Adult↗
PubMed2005

Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management.

The onset of multiple sclerosis (MS) in 85% of young adults is with a subacute clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Whereas multifocal brain lesions are present on MRI in many patients with a CIS, some patients have additional abnormalities on quantitative MRI in otherwise normal-appearing white and grey matter that suggest an extensive pathological process. Functional outcome for patients with symptomatic CIS lesions is determined by the interplay of inflammation, demyelination, axonal damage, remyelination, and cortical adaptation. Recovery of function may be accelerated by high dose corticosteroids, and although interferon beta delays the development of a second relapse, its long-term effect is unknown. A better understanding of pathological and pathogenetic processes in patients with a CIS will facilitate the development of disease-modifying treatments for patients with MS before they become disabled. Continued clinical and laboratory investigation of patients with a CIS should be encouraged.

Disease Management↗
PubMed2005

Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of multiple sclerosis. A proposal for standardization.

The new McDonald diagnostic criteria for multiple sclerosis (MS) incorporate detailed criteria for the interpretation and classification of magnetic resonance imaging (MRI) findings, but, in contrast, provide no instructions for the interpretation of clinical findings. Because MS according to the McDonald criteria is one of the primary endpoints in a large trial enrolling patients after the first manifestation suggestive for a demyelinating disease (BENEFIT study), it was decided to organize a centralized eligibility assessment for this trial. During this eligibility assessment it was observed that there were marked inconsistencies in the decisions of participating neurologists with respect to the classification of clinical symptoms as being caused by one or more lesions provoking discussions in about one in every five patients. This paper describes these inconsistencies and their sources, and recommends a systematic approach that attempts to reduce the variability in interpreting clinical findings.

Adolescent↗
PubMed2005

Relapse rates and enhancing lesions in a phase II trial of natalizumab in multiple sclerosis.

BACKGROUND: Natalizumab, a humanized monoclonal IgG4 antibody, is an alpha4-integrin antagonist, which inhibits the migration of inflammatory cells into the central nervous system, a key pathogenic mechanism in multiple sclerosis (MS). In a six month, phase II clinical trial of patients with relapsing MS, natalizumab significantly reduced the formation of new gadolinium-enhanced (Gd+) lesions and the number of clinical relapses. OBJECTIVE: To investigate the relationship of historical relapse rate and new Gd + lesion number with subsequent MS disease activity and natalizumab treatment in the phase II study. METHODS: Patients who participated in the phase II study were stratified into subgroups according to: (i) the number of relapses in the two years prior to entry into the study: 2 relapses (n = 108), 3 relapses (n =57), and >3 relapses (n =48); (ii) the number of new Gd + lesions at baseline (Month 0): 0 (n = 129), 1-2 (n =50), and >2 (n =33). Relapses and new Gd + lesions during the treatment phase of the trial were determined and compared for each subgroup. RESULTS: Both the prestudy relapse rate and number of new Gd + lesions at baseline were related to the subsequent risk of a relapse; baseline number of Gd + lesions was related to the likelihood of subsequent new Gd + lesion formation. There was a lower proportion of subjects with an on-study relapse and fewer new Gd + lesions in all natalizumab-treated subgroups when compared with their placebo counterpart; the difference was most apparent in the subgroups of patients with >3 relapses in the two years prior to study entry and >2 new Gd -- lesions at Month 0. CONCLUSIONS: There was a lower proportion of subjects with an on-study relapse in natalizumab-treated patients, particularly in those with a more active disease at study entry. Larger ongoing phase III studies will allow more definitive investigation of these preliminary subgroup findings.

Adult↗
PubMed2005

Free gracilis interposition arthroplasty for severe hallux rigidus.

Surgery for the management of hallux rigidus aims to relieve pain and improve function. Arthrodesis, though reliable in terms of pain relief may encounter some resistance from patients reluctant to have a fusion. Results of other techniques, such as silastic implants, may give poor long-term results. Excisional arthroplasty and cheilectomy are also routinely used. Interposition arthroplasty has been used with some success in other joints. We describe a technique of autologous interposition arthroplasty using a free ipsilateral gracilis tendon graft for patients with severe hallux rigidus with moderate to high activity levels and who do not wish to undergo fusion.

Arthroplasty↗
PubMed2005

Minimally invasive hallux valgus correction: a technical note and a feasibility study.

Hallux valgus surgery aims to correct the nonphysiological angulation of the first ray and rebalance its function. Many techniques are reported, each with different indications depending on the pathoanatomy of the deformity. This article presents a minimally invasive distal metatarsal osteotomy technique, requiring no custom instrumentation. The operation is performed under direct vision and without fluoroscopy.

Adult↗
PubMed2004

Identification and activity of a lower eukaryotic serine proteinase inhibitor (serpin) from Cyanea capillata: analysis of a jellyfish serpin, jellypin.

Delineating the phylogenetic relationships among members of a protein family can provide a high degree of insight into the evolution of domain structure and function relationships. To identify an early metazoan member of the high molecular weight serine proteinase inhibitor (serpin) superfamily, we initiated a cDNA library screen of the cnidarian, Cyanea capillata. We identified one serpin cDNA encoding for a full-length serpin, jellypin. Phylogenetic analysis using the deduced amino acid sequence showed that jellypin was most similar to the platyhelminthe Echinococcus multiocularis serpin and the clade P serpins, suggesting that this serpin evolved approximately 1000 million years ago (MYA). Modeling of jellypin showed that it contained all the functional elements of an inhibitory serpin. In vitro biochemical analysis confirmed that jellypin was an inhibitor of the S1 clan SA family of serine proteinases. Analysis of the interactions between the human serine proteinases, chymotrypsin, cathepsin G, and elastase, showed that jellypin inhibited these enzymes in the classical serpin manner, forming a SDS stable enzyme/inhibitor complex. These data suggest that the coevolution of serpin structure and inhibitory function date back to at least early metazoan evolution, approximately 1000 MYA.

Amino Acid Sequence↗
PubMed2004

Reproductive biology: delivering spermatozoan RNA to the oocyte.

Even though the genetic fingerprint of human sperm has been defined, its role in orchestrating fertilization and the development of the early embryo remains vague. Here we show that human male gametes pass over more to the oocyte than just the haploid male genome--paternal messenger RNAs are also delivered to the egg at fertilization. If these transcripts, previously thought to be left-overs from spermatogenesis, are important in early development, our findings may have implications for the success of somatic-cell nuclear transfer in cloning technology and the identification of components leading to unexplained male-factor infertility.

Animals↗
PubMed2004

Environmental versus genetic sex determination: a possible factor in dinosaur extinction?

This study examined the possibility that genetically based sex-determination mechanisms have evolved to ensure a balanced male/female ratio and that this temperature-independent checkpoint might have been unavailable to long-extinct reptiles, notably the dinosaurs. A review of the literature on molecular and phylogenetic relationships between modes of reproduction and sex determination in extant animals was conducted. Mammals, birds, all snakes and most lizards, amphibians, and some gonochoristic fish use specific sex-determining chromosomes or genes (genetic sex determination, GSD). Some reptiles, however, including all crocodilians studied to date, many turtle and tortoise species, and some lizards, use environmental or temperature-dependent sex determination (TSD). We show that various modes of GSD have evolved many times, independently in different orders. Animals using TSD would be at risk of rapid reproductive failure due to a skewed sex ratio favoring males in response to sustained environmental temperature change and favoring the selection of sex-determining genes. The disadvantage to the evolving male sex-determining chromosome, however, is its decay due to nonrecombination and the subsequent loss of spermatogenesis genes. Global temperature change can skew the sex ratio of TSD animals and might have played a significant role in the demise of long-extinct species, notably the dinosaurs, particularly if the temperature change resulted in a preponderance of males. Current global warming also represents a risk for extant TSD species.

Animals↗
PubMed2004

Monkeypox virus detection in rodents using real-time 3'-minor groove binder TaqMan assays on the Roche LightCycler.

During the summer of 2003, an outbreak of human monkeypox occurred in the Midwest region of the United States. In all, 52 rodents suspected of being infected with monkeypox virus were collected from an exotic pet dealer and from private homes. The rodents were euthanized and submitted for testing to the United States Army Medical Research Institute of Infectious Diseases by the Galesburg Animal Disease Laboratory, Illinois Department of Agriculture. The rodent tissue samples were appropriately processed and then tested by using an integrated approach involving real-time polymerase chain reaction (PCR) assays, an antigen-detection immunoassay, and virus culture. We designed and extensively tested two specific real-time PCR assays for rapidly detecting monkeypox virus DNA using the Vaccinia virus F3L and N3R genes as targets. The assays were validated against panels of orthopox viral and miscellaneous bacterial DNAs. A pan-orthopox electrochemiluminescence (ECL) assay was used to further confirm the presence of Orthopoxvirus infection of the rodents. Seven of 12 (58%) animals (seven of 52 (15%) of all animals) tested positive in both monkeypox-specific PCR assays and two additional pan-orthopox PCR assays (in at least one tissue). The ECL results showed varying degrees of agreement with PCR. One hamster and three gerbils were positive by both PCR and ECL for all tissues tested. In addition, we attempted to verify the presence of monkeypox virus by culture on multiple cell lines, by immunohistology, and by electron microscopy, with negative results. Sequencing the PCR products from the samples indicated 100% identity with monkeypox virus strain Zaire-96-I-16 (a human isolate from the Congo). These real-time PCR and ECL assays represent a significant addition to the battery of tests for the detection of various orthopoxviruses. In light of the recent monkeypox virus transmissions, early detection of the virus is crucial for both natural outbreaks and potential acts of bioterrorism.

Animals↗
PubMed2004

Smallpox and pan-orthopox virus detection by real-time 3'-minor groove binder TaqMan assays on the roche LightCycler and the Cepheid smart Cycler platforms.

We designed, optimized, and extensively tested several sensitive and specific real-time PCR assays for rapid detection of both smallpox and pan-orthopox virus DNAs. The assays are based on TaqMan 3'-minor groove binder chemistry and were performed on both the rapid-cycling Roche LightCycler and the Cepheid Smart Cycler platforms. The hemagglutinin (HA) J7R, B9R, and B10R genes were used as targets for the variola virus-specific assays, and the HA and DNA polymerase-E9L genes were used as targets for the pan-orthopox virus assays. The five orthopox virus assays were tested against a panel of orthopox virus DNAs (both genomic and cloned) at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). The results indicated that each assay was capable of detecting both the appropriate cloned gene and genomic DNA. The assays showed no cross-reactivity to the 78 DNAs in the USAMRIID bacterial cross-reactivity panel. The limit of detection (LOD) of each assay was determined to be between 12 and 25 copies of target DNA. The assays were also run against a blind panel of DNAs at the Centers for Disease Control and Prevention (CDC) on both the LightCycler and the Smart Cycler. The panel consisted of eight different variola virus isolates, five non-variola virus orthopox virus isolates, two varicella-zoster virus isolates, and one herpes simplex virus isolate. Each sample was tested in triplicate at 2.5 ng, 25 pg, 250 fg, and 2.5 fg, which represent 1.24 x 10(7), 1.24 x 10(5), 1.24 x 10(3), and 1.24 x 10(1) genome equivalents, respectively. The results indicated that each of the five assays was 100% specific (no false positives) when tested against both the USAMRIID panels and the CDC blind panel. With the CDC blind panel, the LightCycler was capable of detecting 96.2% of the orthopox virus DNAs and 93.8% of the variola virus DNAs. The Smart Cycler was capable of detecting 92.3% of the orthopox virus DNAs and between 75 and 93.8% of the variola virus DNAs. However, all five assays had nearly 100% sensitivity on both machines with samples above the LOD (>12 gene copies). These real-time PCR assays represent a battery of tests to screen for and confirm the presence of variola virus DNA. The early detection of a smallpox outbreak is crucial whether the incident is an act of bioterrorism or an accidental occurrence.

Base Sequence↗
PubMed2004

The smart wheelchair component system.

While the needs of many individuals with disabilities can be satisfied with power wheelchairs, some members of the disabled community find it difficult or impossible to operate a standard power wheelchair. To accommodate this population, several researchers have used technologies originally developed for mobile robots to create "smart wheelchairs" that reduce the physical, perceptual, and cognitive skills necessary to operate a power wheelchair. We are developing a Smart Wheelchair Component System (SWCS) that can be added to a variety of commercial power wheelchairs with minimal modification. This paper describes the design of a prototype of the SWCS, which has been evaluated on wheelchairs from four different manufacturers.

Electric Power Supplies↗
PubMed2003

Mutational analysis of the Acropora millepora PaxD paired domain highlights the importance of the linker region for DNA binding.

Pax transcription factors are found in animals, from simple sponges to insects and vertebrates. The defining feature of Pax proteins is the DNA-binding paired domain (PD), which consists of two helix-turn-helix subdomains, joined with a linker region. Despite high specificity in vivo, the paired domains of different Pax proteins bind similar consensus DNA sequences in vitro. Using bandshift techniques, we show here that the paired domain of the Acropora millepora PaxD protein, which unambiguously belongs to the Pax3/7 group, does not bind to three defined paired domain-binding sites. Domain swapping experiments and site-directed mutagenesis identified two amino acid residues in the linker region of the paired domain as critical to DNA binding; G70 and S71 are highly conserved in Pax proteins, but differ in PaxD (L70 and N71). The PaxD data thus highlight the importance of the linker region, and particularly G70 and S71, in DNA binding by Pax proteins.

Amino Acid Sequence↗
PubMed2003

Quantitative CT indexes in idiopathic pulmonary fibrosis: relationship with physiologic impairment.

PURPOSE: To determine whether measurements of skewness, kurtosis, and mean lung attenuation on thin-section computed tomographic (CT) histograms in patients with idiopathic pulmonary fibrosis (IPF) correlate with pulmonary physiologic abnormality in a nonspirometrically controlled multicenter study. MATERIALS AND METHODS: The authors analyzed baseline digital thin-section CT data from 144 patients with IPF who enrolled in a double-blind placebo-controlled clinical effectiveness trial of interferon beta 1a in the treatment of IPF. All patients underwent thin-section CT in the supine position at full inspiration. The lungs were isolated by using a semiautomated thresholding technique, with an upper threshold of -200 HU. An attenuation correction algorithm was used. Pulmonary function tests (PFTs) included forced vital capacity, total lung capacity, forced expiratory volume in 1 second, and diffusing lung capacity. Univariate and multiple correlation and regression statistical analyses were used to determine relationships between histogram features and results of PFTs. RESULTS: Moderate correlations existed between histogram features and PFT results. Kurtosis showed the greatest degree of correlation with physiologic abnormality (r = 0.53, P <.01). Strength of correlation increased with exclusion of suboptimal scans but did not change significantly after application of an attenuation correction algorithm. Attenuations for lungs, gas, and soft tissue varied considerably between scanner manufacturers. Kurtosis alone provided predictions of pulmonary function that were virtually as good as those from all histogram features combined. CONCLUSION: Thin-section CT histograms of the lungs were found to correlate with results of PFTs in patients with IPF, which supports the claim that histogram features can be used as valid indexes of IPF in a multiinstitutional nonspirometrically controlled study.

Algorithms↗
PubMed2003

Understanding the accommodating intraocular lens.

PURPOSE: To review current accommodating intraocular lens (IOL) designs and introduce a new design consisting of a plus lens and a minus lens. SETTING: Cornea Consultants of Boston, Boston, Massachusetts, USA. METHODS: Computer simulation studies of a model eye calculated the pseudoaccommodation range with different powers of 1 IOL or of 2 IOLs acting as a doublet. RESULTS: The doublet consisting of a convex (plus) lens and a concave (minus) lens gave a greater range of power change than a single convex lens or a doublet consisting of 2 convex lenses. The greater range of power results from the plus lens moving forward. CONCLUSION: The results show that an IOL design consisting of positive and negative lenses that move closer or farther from each other offers a greater range of pseudoaccommodation than other designs.

Accommodation, Ocular↗